[Molecular mechanisms underlying the development and spread of antibiotic resistance]

Antibiotics are characterized by their selective toxicity against bacterial pathogens. Due to the high genetic flexibility of bacteria, which includes mutations in their own genes as well as the uptake of foreign genes from other species, pathogens can rapidly adapt, for example, by altering molecular target structures. This article provides an overview of the molecular basis of important, clinically relevant mechanisms of resistance to antibiotics and describes the ways for transfer of the genes involved.The emergence of antibiotic-resistant mutants can be essentially explained by three fundamental molecular mechanisms: (1) alteration of the binding site for an antibiotic, (2) reduction of the antibiotic concentration at the binding site, and (3) enzymatic modification of the antibiotic. Depending on the molecular structure of the antibiotic, its interaction with the target structure, and the genetic makeup of the respective pathogen, numerous variations of these three mechanisms exist.To select an appropriate therapy in the presence of antibiotic resistance, the knowledge of the underlying resistance mechanism, the timely identification of the responsible pathogen and its susceptibility to alternative antibiotics are necessary. A fundamental disadvantage of chemically defined antibiotics is their inability to structurally adapt to conditions altered by the acquisition of resistance. In addition to reducing selective pressure and maintaining hygienic standards, the use of bacteriophages represents a promising alternative. As "biological agents," phages can adapt to phage-resistant bacterial mutants during therapy through genetic changes.